Molecular constituents of maxi K<sub>Ca</sub> channels in human coronary smooth muscle: predominant <i>α</i>+<i>β</i> subunit complexes

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<jats:p> <jats:list list-type="explicit-label"> <jats:list-item><jats:p>Human large‐conductance voltage‐ and calcium‐sensitive K<jats:sup>+</jats:sup> (maxi K<jats:sub>Ca</jats:sub>) channels are composed of at least two subunits: the pore‐forming subunit, <jats:italic>α</jats:italic>, and a modulatory subunit, <jats:italic>β.</jats:italic> Expression of the <jats:italic>β</jats:italic> subunit induces dramatic changes in α subunit function. It increases the apparent Ca<jats:sup>2+</jats:sup> sensitivity and it allows dehydrosoyasaponin I (DHS‐I) to upregulate the channel.</jats:p></jats:list-item> <jats:list-item><jats:p>The functional coupling of maxi K<jats:sub>Ca</jats:sub> channel <jats:italic>α</jats:italic> and <jats:italic>β</jats:italic> subunits in freshly dissociated human coronary smooth muscle cells was assessed. To distinguish maxi K<jats:sub>Ca</jats:sub> currents modulated by the <jats:italic>β</jats:italic> subunit, we examined (a) their apparent Ca<jats:sup>2+</jats:sup> sensitivity, as judged from the voltage necessary to half‐activate the channel (<jats:italic>V</jats:italic><jats:sub>1/2</jats:sub>), and (b) their activation by DHS‐I.</jats:p></jats:list-item> <jats:list-item><jats:p>In patches with unitary currents, the majority of channels were half‐activated near –85 mV at 18 <jats:italic>μ</jats:italic><jats:sc>m</jats:sc> Ca<jats:sup>2+</jats:sup>, a value similar to that obtained when the human K<jats:sub>Ca</jats:sub> channel α (HSLO) and <jats:italic>β</jats:italic> (HK<jats:sub>VCa</jats:sub>β) subunits are co‐expressed. A small number of channels half‐activated around 0 mV, suggesting the activity of the <jats:italic>α</jats:italic> subunit alone.</jats:p></jats:list-item> <jats:list-item><jats:p>The properties of macroscopic currents were consistent with the view that most pore‐forming <jats:italic>α</jats:italic> subunits were coupled to <jats:italic>β</jats:italic> subunits, since the majority of currents had values for <jats:italic>V</jats:italic><jats:sub>1/2</jats:sub> near to –90 mV, and currents were potentiated by DHS‐I.</jats:p></jats:list-item> <jats:list-item><jats:p>We conclude that in human coronary artery smooth muscle cells, most maxi K<jats:sub>Ca</jats:sub> channels are composed of <jats:italic>α</jats:italic> and <jats:italic>β</jats:italic> subunits. The higher Ca<jats:sup>2+</jats:sup> sensitivity of maxi K<jats:sub>Ca</jats:sub> channels, resulting from their coupling to <jats:italic>β</jats:italic> subunits, suggests an important role of this channel in regulating coronary tone. Their massive activation by micromolar Ca<jats:sup>2+</jats:sup> concentrations may lead to a large hyperpolarization causing profound changes in coronary blood flow and cardiac function.</jats:p></jats:list-item> </jats:list> </jats:p>

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